The overall goal of the this project is to understand how cells and tissues respond to environmental stress. Glucocorticoids, a primary stress response hormone released following the activation of the hypothalamic pituitary adrenal axis. Chronic evaluation of glucocorticoids due to prolonged stress and/or chronic therapeutic intervention with glucocorticoids has numerous detrimental actions on human health and studying their actions and signaling pathways is critical to the mission of NIEHS. We seek to understand how glucocorticoids signal in a cell specific manner in order to provide insights and discoveries concerning their actions on cell growth, differentiation and cell death. These hormones regulate numerous aspects of physiology including glucose homeostasis, protein metabolism, skeletal growth, connective tissue metabolism, respiratory function, immune surveillance and components of human behavior. This diversity of actions has made glucocorticoids attractive for therapeutic development and, as a class of compounds, they are among the most prescribed drugs in the world. They remain a primary treatment for the environmental disease, asthma, as well as a host of other inflammatory conditions in humans.